The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects

Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches.

Treatment with intralesional methotrexate injection in a patient with nail psoriasis

Psoriasis vulgaris is an inflammatory skin disease involving the skin, nails, and joints. While nail involvement is observed in 70–80% of patients with psoriasis, the rate of patients with isolated nail involvement is 5–10%. Dystrophies arising in the nails in psoriasis affect the patient’s quality of life, and local and systemic therapies may be used as treatment. Intralesional methotrexate or corticosteroid injection might be an option in the treatment of patients with the involvement of one nail or some nails or without the involvement of the skin and joints, due to the side effects of systemic and biological agents. Herein, we report a female patient with nail psoriasis resistant to a previously applied topical treatment, the efficacy of intralesional methotrexate without the use of a systemic antipsoriatic agent, and no progression of side effects.

IL-36γ promotes psoriasis-like features in keratinocytes in an imiquimod-induced murine model of psoriasis

IntroductionPsoriasis is a recurrent, chronic inflammatory skin disease with complex pathogenesis. The disease imposes a heavy burden on patients. Interleukin (IL)-36γ belongs to the IL-36 family and is predominantly expressed by epithelial cells. IL-36γ is upregulated in psoriasis lesions. However, the effects of IL-36γ in keratinocytes remain unclear.Material and methodsEighteen IL-36γ-deficient mice were divided into three groups: the vaseline group, the imiquimod (IMQ) group, and the IMQ/IL-36γ group. Vaseline or IMQ was administered for 6 consecutive days. The severity of psoriasis-like lesions was evaluated using a modified Psoriasis Area and Severity Index (PASI) scoring system. Production of cytokines and expression of differentiation markers were assessed by immunohistochemistry.ResultsIMQ-induced psoriasis lesions were significantly more severe in IMQ/IL-36γ-treated mice compared with vaseline-treated and IMQ-treated mice, as shown by an exacerbated inflammatory phenotype, increased numbers of blood vessels, increased infiltration of cells, and increased epidermal thickness. Expression of loricrin and keratin 5 in skin lesions was decreased following treatment with IL-36γ. Levels of IL-17A, interferon-γ, β-catenin and Dickkopf-related protein 1 were elevated in keratinocytes within psoriatic lesions following IL-36γ stimulation.ConclusionsTogether, these data showed that IL-36γ contribute to abnormal keratinocytes proliferation and keratinocyte-related proinflammatory cytokines, and suggest that IL-36γ may play an important role in the pathogenesis of psoriasis.

Different Approaches to Atopic Dermatitis by Allergists, Dermatologists, and Pediatricians

Objectives. Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease, with a vast drug arsenal and guidelines available for its management and diagnosis and different medical specialties engaged in providing care. This study aimed to outline the therapeutic and diagnostic approaches to the AD of allergists, dermatologists, and pediatricians and verify whether they are compliant with the guidelines. Methods. A cross-sectional study using an electronic questionnaire administered through the SurveyMonkey® platform was disclosed by participating medical societies to their medical associates. Results. Of the 1,473 participating physicians, the use of moisturizers as part of AD treatment was observed among pediatricians (91.9%), dermatologists (97.5%), and allergists (100%; p = 0.07 ). The preference for the use of new emollients was lower among pediatricians (57%) than dermatologists (75.9%) and allergists (71.4%; p < 0.001 ). The prevalence of wet-wrap therapy was lower among dermatologists (16.3%) than allergists (51%; p < 0.001 ). The recommendation of proactive treatment with topical corticosteroids was more frequently reported by allergists (65.3%) than pediatricians (43.3%) and dermatologists (40.8%; p < 0.001 ), and the same trend was observed in relation to proactive treatment using calcineurin inhibitors. The use of oral anti-histamines to control pruritus was mainly considered by pediatricians (69.2%) and dermatologists (59.2% p < 0.001 ). Clinical experience with systemic immunomodulating agents was greater among allergists (77.5%) and dermatologists (60.8%; p < 0.001 ), with cyclosporine being the most cited systemic immunomodulating agent. Environmental control of aeroallergens was recommended by pediatricians (89.8%), dermatologists (86.9%), and allergists (100%; p = 0.01 ). Conclusion. There were differences in the therapeutic and diagnostic approaches to AD used by allergists, dermatologists, and pediatricians and those recommended by the guidelines, especially regarding the use of wet-wrap therapy, proactive treatment with topical corticosteroids or calcineurin inhibitors, prescription of anti-histamines, recommendation of phototherapy, and control of aeroallergens.

Treatment and Management of Psoriasis: A review

Psoriasis is a common, chronic inflammatory skin disease affecting many people of the world now a days. Psoriasis is principally an immunological T lymphocyte-driven disease, relating both the distinctive and T-cell-mediated immune systems. The mostly affected sites comprise the scalp, extensor surfaces of the knees and elbows, umbilicus, genitalia, anterior lower legs and nails. This disease can significantly impact on a patient's quality of life and is connected co-morbidities comprise psoriatic arthritis, obesity and the metabolic syndrome, diseases of cardiovascular system and liver with fats. Provided treatment is depends on disease severity, quality of life, patient preference, relevant co-morbidities and efficacy of the treatment. Treatment such as topical emollients, tar, analogues of vitamin D and corticosteroids are first line for local/mild disease. Psoriasis cannot be fully cured once it affects a person but can be managed by proper taking care of the skin according to the doctors. Patient counseling can also add benefits in the management of psoriasis.

The Antidiabetic Agent Metformin Inhibits IL-23 Production in Murine Bone-Marrow-Derived Dendritic Cells

Psoriasis is a chronic inflammatory skin disease, and its immune mechanism has been profoundly elucidated. Biologics targeting interleukin (IL)-23 have prevented the development of psoriasis. As major sources of IL-23, dendritic cells (DCs) play a pivotal role in psoriasis; however, the regulatory mechanism of IL-23 in DCs remains unclear. IL-36γ was reported to reflect the disease activity of psoriasis. Therefore, we hypothesized that IL-36γ may affect IL-23 production in DCs. To reveal the mechanism by which IL-36γ controls IL-23 production in DCs, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-36γ. IL-36γ stimulation upregulated the mRNA and protein expression of Nfkbiz in BMDCs. Nfkbiz knockdown using siRNA transfection partially inhibited the upregulation of IL-23 mRNA expression induced by IL-36γ stimulation. Since NF-κB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-κB signaling, we examined the effect of metformin treatment on IL-36γ-induced IL-23 production. Metformin treatment impaired the phosphorylation of NF-κB induced by IL-36γ stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs. These data provided evidence that metformin treatment can inhibit IL-36γ-mediated IL-23 production in BMDCs, which might contribute to the prevention of psoriasis.

Cognitive Process of Psoriasis and Its Comorbidities: From Epidemiology to Genetics

Psoriasis (PsO) is a chronic inflammatory skin disease that affects approximately 2% of the population all over the world. Comorbidities of PsO have increasingly garnered more interest in the past decades. Compared with the normal population, the incidences of comorbidities are higher among patients with PsO. In the last 20 years, researchers have focused on studying the genetic components of PsO, and genetic associations between PsO and its comorbidities were elucidated. This review provides an in-depth understanding and summarization of the connection between PsO and its comorbidities from the perspectives of epidemiology and genetics. Further understanding of PsO and its comorbidities will promote research on the pathogenesis, drug development, novel therapy methods, and personalized and precision treatment of PsO and its comorbidities.

Serum-Derived Neuronal Exosomal microRNAs as Stress-Related Biomarkers in an Atopic Dermatitis Model

Chronic allergic inflammatory skin disease—atopic dermatitis (AD)—is characterized by eczema, pruritus, xeroderma, and lichenification. Psychological stress is one cause of this disease; however, psychological stress will also result from the presence of AD symptoms. Previous studies have shown that psychological stress triggers neuroinflammation in the brain, where microRNAs (miRNAs) in the neuronal exosomes (nEVs) were analyzed to identify the composition of the miRNAs in the nEVs and how they were altered by AD. In this study, the AD model was induced by treatment with 2,4-dinitrochlorobenzene (DNCB). The expression patterns of neuroinflammation markers, such as brain-derived neurotrophic factor, cyclooxygenase-2, and glial fibrillary acidic protein, were subsequently evaluated over time. Among these groups, there was a significant difference in DNCB 14 days expression compared with the control; therefore, nEVs were isolated from serum and next-generation sequencing was performed. The results demonstrate that 9 miRNAs were upregulated and 16 were downregulated in the DNCB 14 days compared with the control. Previous studies have shown that some of these miRNAs are associated with stress and stress-induced depression, which suggests that the miRNAs in nEVs may also be stress-related biomarkers.

A New Formulation of Probiotics Attenuates Calcipotriol-Induced Dermatitis by Inducing Regulatory Dendritic Cells

Atopic dermatitis (AD) is a recurrent chronic inflammatory skin disease affecting up to 30% of the children population, and immuno-regulatory therapy that could modify the course of disease is urgently needed. Probiotics have demonstrated therapeutic effects on AD and could potentially regulate the disease process. However, the efficacy of probiotics for AD is inconsistent among different studies, which is mainly due to the elusive mechanism and different species and (or) strains used. In this study, we designed a mixture of five strains of probiotics (named IW5) and analyzed the effect and mechanism of IW5 on calcipotriol (MC903)-induced AD-like dermatitis. We found that IW5 significantly alleviated skin inflammation of the MC903-induced AD in mice. Administration with IW5 induced increased production of regulatory T cells and regulatory dendritic cells (DCregs) in the mesenteric lymph nodes. We also found that the diversity of the gut microbiota in the mice with MC903-induced dermatitis was increased after IW5 administration, and the level of butyrate in the gut was elevated. In cell culture, butyrate induced the production of DCregs. Our study revealed the therapeutic effects of a newly designed probiotics mixture and uncovered a possible mechanism, providing a foundation for future clinical studies.

Increased Serum Levels of S100A4 and S100A15 in Individuals Suffering from Hidradenitis Suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Recently, some S100 proteins have been suggested to play an important role in the pathogenesis of chronic immune-mediated inflammatory diseases and they may constitute valuable biomarkers for these diseases’ diagnosis and monitoring. The objective of the current study was to investigate, for the first time, serum levels of S100A4 and S100A15 in individuals suffering from HS. Furthermore, we assessed the associations between S100A4 and S100A15 serum levels and the severity of disease, CRP serum concentration and some demographic and clinical data. Serum levels of S100A4 and S100A15 were evaluated with the commercially available ELISA kit according to the manufacturer’s instructions. The serum level of S100A4 in individuals with HS was significantly elevated as compared to controls, with the highest level found in the individuals in Hurley stage II. The S100A15 serum level was positively correlated with the CRP concentration and was associated with the severity of the disease. The serum level of S100A15 in the individuals in Hurley stage III was significantly elevated compared to that of the controls and the individuals with HS in Hurley stages I and II. S100A4 and S100A15 may be considered as new serum biomarkers for the monitoring of HS progression, and they may play a role in the pathogenesis of HS by promoting inflammatory process and fibrosis.